Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors.

Abstract

This study was conducted to compare long-term outcomes in patients with refractory/relapsed grades 1 and 2 follicular lymphoma (FL) after allogeneic (allo) versus autologous (auto) hematopoietic cell transplantation (HCT) in the rituximab era. Adult patients with relapsed/refractory grades 1 and 2 FL undergoing first reduced-intensity allo-HCT or first autograft during 2000 to 2012 were evaluated. A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger and more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto-HCT versus allo-HCT groups for nonrelapse mortality (NRM) were 5% versus 26% (P < .0001); relapse/progression: 54% versus 20% (P < .0001); progression-free survival (PFS): 41% versus 58% (P < .001), and overall survival (OS): 74% versus 66% (P = .05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months after HCT (relative risk [RR], 4.4; P < .0001) and worse PFS (RR, 2.9; P < .0001) beyond 11 months after HCT. In the first 24 months after HCT, auto-HCT was associated with improved OS (RR, .41; P < .0001), but beyond 24 months, it was associated with inferior OS (RR, 2.2; P = .006). A landmark analysis of patients alive and progression-free at 2 years after HCT confirmed these observations, showing no difference in further NRM between both groups, but there was significantly higher risk of relapse/progression (RR, 7.3; P < .0001) and inferior PFS (RR, 3.2; P < .0001) and OS (RR, 2.1; P = .04) after auto-HCT. The 10-year cumulative incidences of second hematological malignancies after allo-HCT and auto-HCT were 0% and 7%, respectively. Auto-HCT and reduced-intensity-conditioned allo-HCT as first transplantation approach can provide durable disease control in grades 1 and 2 FL patients. Continued disease relapse risk after auto-HCT translates into improved PFS and OS after allo-HCT in long-term survivors.

• Authors: Evgeny Klyuchnikov, Ulrike Bacher, Nicolaus M Kröger, Parameswaran N Hari, Kwang Woo Ahn, Jeanette Carreras, Veronika Bachanova, Asad Bashey, Jonathon B Cohen, Anita D'Souza, César O Freytes, Robert Peter Gale, Siddhartha Ganguly, Mark S Hertzberg, Leona A Holmberg, Mohamed A Kharfan-Dabaja, Andreas Klein, Grace H Ku, Ginna G Laport, Hillard M Lazarus, Alan M Miller, Alberto Mussetti, Richard F Olsson, Shimon Slavin, Saad Z Usmani, Ravi Vij, William A Wood, David G Maloney, Anna M Sureda, Sonali M Smith, Mehdi Hamadani
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 21 Issue 12 Pg. 2091-2099 (Dec 2015) ISSN: 1523-6536 [Electronic] United States
• PMID: 26253007 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Myeloablative Agonists
• Rituximab

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Disease Progression
• Drug Resistance, Neoplasm
• Female
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Longitudinal Studies
• Lymphoma, Follicular (immunology, mortality, pathology, therapy)
• Male
• Middle Aged
• Myeloablative Agonists (therapeutic use)
• Neoplasm Grading
• Recurrence
• Rituximab (therapeutic use)
• Survival Analysis
• Survivors
• Transplantation Conditioning (methods)
• Transplantation, Autologous
• Transplantation, Homologous
• Treatment Outcome